PROJECT SUMMARY/ABSTRACT A significant number of individuals with neurodevelopmental disorders demonstrate impairments in expressive language, and these impairments have persistent, lifelong effects on development and adaptive behavior. Two neurodevelopmental disorders particularly impacted by language impairments include autism spectrum disorders (ASD) and fragile X syndrome (FXS). ASD affects 1 in 68 individuals, and while etiology is presently unknown, there is a strong genetic component. Fragile X is the most common inherited form of intellectual disability and has a high comorbidity with ASD. Children with ASD and FXS have impairments in language across a number of different domains, including semantics and grammar; however, we do not fully understand the nature of language impairment in these domains, and in particular the impact of ASD on language in FXS. A key component within this line of work involves the integration of neuroimaging methods with behavioral measures of language, in order to identify the key neural substrates associated with language in these complex disorders, but to date this has not been done in FXS. The training and research in this proposal addresses these significant gaps in the field by combining behavioral and neuroimaging methods to address two specific aims: 1) Compare the structural language profiles in children with FXS, with and without ASD, and children with idiopathic ASD, and 2) Examine the neural substrates in FXS and ASD and their association with behavioral language measures. We will recruit three groups of school-age boys, specifically boys with FXS- only (n = 15); boys with FXS and ASD (n = 15), and boys with idiopathic ASD (n = 15). The proposed project represents an innovative design, combining a careful behavioral phenotype with imaging measures of brain volume, white matter microstructure and functional connectivity. The proposed career development and results from the specific aims will allow the investigator to become an independent scientist, by broadening her training to include neuroimaging methods and analyses and developing a plan to adapt the scanning environment to meet the needs of individuals with neurodevelopmental disorders. The results will inform hypotheses regarding the relationship between language in neurodevelopmental disorders and the corresponding neural substrates. This information will be used to develop future projects to determine the longitudinal course of language development, the impact of ASD on this genetic disorder, and the neuroplasticity of the associated neural substrates impacted in these disorders.